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DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage

Naoe Taira1, Keishi Nihira, Tomoko Yamaguchi

  • 1Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8510, Japan.

Molecular Cell
|March 14, 2007
PubMed

Insights

Dual-specificity tyrosine-phosphorylation-regulated kinase 2 (DYRK2) directly phosphorylates p53 at Ser46, a key step in DNA damage-induced apoptosis. DYRK2 nuclear translocation triggers p53AIP1 expression, committing cells to programmed cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Genotoxic stress activates tumor suppressors like p53, crucial for DNA damage response.
  • p53 regulates cell cycle arrest and apoptosis, but the mechanisms for committing to apoptosis are unclear.
  • Phosphorylation of p53 at Ser46 is linked to apoptosis induction via p53AIP1, yet the responsible kinases remain unidentified.

Purpose of the Study:

  • To identify the kinase responsible for p53 Ser46 phosphorylation.
  • To elucidate the role of this kinase in p53-mediated apoptosis following genotoxic stress.

Main Methods:

  • Investigated the kinase activity of DYRK2 on p53.
  • Examined DYRK2 localization and function upon genotoxic stress.
  • Assessed the impact of DYRK2 on p53AIP1 expression and apoptosis.

Main Results:

  • Demonstrated that DYRK2 directly phosphorylates p53 at Ser46.
  • Showed that DYRK2 translocates to the nucleus upon genotoxic stress to perform this phosphorylation.
  • Confirmed that DYRK2 induces p53AIP1 expression and apoptosis in a Ser46-dependent manner.

Conclusions:

  • DYRK2 is identified as a key kinase that phosphorylates p53 at Ser46.
  • DYRK2 plays a critical role in regulating p53-dependent apoptosis in response to DNA damage.

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